Conclusion
These findings suggest that semaglutide may mitigate cardiomyocyte injury caused by a high-fat diet through regulation of HDLSDSLEP-1 expression. These discoveries are expected to unveil novel molecular mechanisms and provide new targets for clinical treatment.
Methods
Mouse models of obesity were established with semaglutide treatment. Palmitic acid-cultured mouse cardiomyocytes with HSDL2 knockout were used, as well as palmitic acid-induced high-fat environment models followed by semaglutide treatment. The levels of inflammatory and oxidative stress markers in serum and cardiomyocytes were measured. Additionally, the expression of HSDL2 and autophagy levels in different cell groups were assessed to evaluate the effect of semaglutide on high-fat diet-induced cardiomyocyte injury mediated by HSDL2.
Results
Obesity increased oxidative stress, which was alleviated by intervention with semaglutide. Furthermore, semaglutide down-regulated HSDL2 expression in obese individuals. Moreover, palmitic acid-induced oxidative stress and autophagy were reduced when using cells with knocked out HSDL2 gene.